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Intravenous anesthetics have marked effects on memory function, even at subclinical concentrations. Fundamental questions remain in characterizing anesthetic amnesia and identifying affected system-level processes. The authors applied a mathematical model to evaluate time-domain components of anesthetic amnesia in human subjects.Sixty-one volunteers were randomized to receive propofol (n = 12), thiopental (n = 13), midazolam (n = 12), dexmedetomidine (n = 12), or placebo (n = 12). With drug present, subjects encoded pictures into memory using a 375-item continuous recognition task, with subsequent recognition later probed with drug absent. Memory function was sampled at up to 163 time points and modeled over the time domain using a two-parameter, first-order negative power function. The parietal event-related P2–N2 complex was derived from electroencephalography, and arousal was repeatedly sampled. Each drug was evaluated at two concentrations.The negative power function consistently described the course of amnesia (mean R2 = 0.854), but there were marked differences between drugs in the modulation of individual components (P < 0.0001). Initial memory strength was a function of arousal (P = 0.005), whereas subsequent decay was related to the reaction time (P < 0.0001) and the P2–N2 complex (P = 0.007/0.002 for discrete components).In humans, the amnesia caused by multiple intravenous anesthetic drugs is characterized by arousal-related effects on initial trace strength, and a subsequent decay predicted by attenuation of the P2–N2 complex at encoding. The authors propose that the failure of normal memory consolidation follows drug-induced disruption of interregional synchrony critical for neuronal plasticity and discuss their findings in the framework of memory systems theory.